Prosthetic heart valves are used to replace damaged or diseased heart valves. Prosthetic heart valves may be used to replace a heart's natural valves including aortic, mitral, and pulmonary valves. The predominant types of prosthetic heart valves are either mechanical valves or bioprosthetic valves. Bioprosthetic valves include allograft valves, which include biomaterial supplied from human cadavers; autologous valves, which include biomaterial supplied from the individual receiving the valve; and xenograft valves, which include biomaterial obtained from non-human biological sources including pigs, cows or other animals.
Presently, mechanical valves have the longest durability of available replacement heart valves. However, implantation of a mechanical valve requires a recipient to be prescribed anticoagulants to prevent formation of blood clots. Unfortunately, continuous use of anticoagulants can be dangerous, as it greatly increases the user's risk of serious hemorrhage. In addition, a mechanical valve can often be audible to the recipient and may fail without warning, which can result in serious consequences, even death.
The use of bioprosthetic heart valves (BHVs) in valve replacement procedures is often preferred as BHVs do not require ongoing patient treatment with anticoagulants. Allograft transplants have been quite effective, with good compatibility and blood flow characteristics in the recipients. However, the availability of human valves for transplantation continues to decline as a percentage of cardiac surgeries performed each year. As such, the choice of xenograft materials for use in replacement BHVs is becoming more common.
Both xenografts and allografts require that the graft biomaterial be chemically fixed, or cross-linked, prior to use, in order to render the biomaterial non-antigenic as well as improve resistance to degradation. Currently, glutaraldehyde fixation of xenograft or allograft biomaterial is commonly used. Glutaraldehyde fixation forms covalent cross-links between free amines in the tissue proteins. As a result, the tissue is less susceptible to adverse immune reactions by the patient. Fixation is also believed to improve the valve durability by making the tissue stronger and less susceptible to enzymatic degradation.
One disadvantage of current xenograft materials is poor durability. At present, conventional xenograft valves require replacement within five to ten years of the original repair. This is at least in part due to the fact that xenografts, particularly those chemically fixed with glutaraldehyde, are stiffer and less pliable than the recipient's original valve. As a consequence of the increased stiffness, the periodic opening and closing of the valve leads to material fatigue of the bioprosthetic replacement tissue. In addition, the recipient's heart will be required to work harder to overcome the stiffness of the bioprosthetic valve as compared to the exertion required for the original valve to function. As the material integrity of the xenograft valve is lessened over time, the efficiency of the valve operation also decreases. Additionally, fatigue and mechanical degradation of the xenograft valve is associated with increased calcification of the valve. The calcification causes additional stiffening which further degrades the physical and biological integrity of the valve.
One form of a conventional bioprosthetic tissue valve comprises a stent which may be in the form of a rigid, annular ring portion onto which separate leaflets of fixed bovine or porcine pericardium are attached. The leaflets are sewn together so as to provide a movement similar to that of an actual heart valve. Unfortunately, due to the heterogenic nature of the pericardium, the pericardium source material used to form the BHV leaflets can have notable variations in physical properties, even when harvested from the same pericardial sac. For example, Simionescu et al. (Mapping of Glutaraldehyde-treated Bovine Pericardium and Tissue Selection for Bio-Prosthetic Heart Valves, Journal of Biomedical Materials Research, 27(6), 697, 1993, which is incorporated herein by reference) discusses differences in individual pericardium sacs with respect to fiber orientation, suture holding power, and thickness. In an effort to form more homogeneous bio-prosthetic heart valve leaflets, it has been suggested that individual heart valve leaflets be tested and evaluated prior to BHV formation so as to use leaflets having similar properties, such as similar deflection values (see, for example, U.S. Pat. No. 6,413,275 B1, which is incorporated herein by reference).
Despite these advances in addressing the needs for longer lasting and better performing BHVs, there remains room for variation and improvement within the art.